This invention relates to treatment of conditions associated with bladder hypersensitivity, and conditions associated with a poorly functioning bladder.
European Journal of Pharmacology 146 (1988), 187-188, and Naunyn-Schmiedeberg""s Arch. Pharmacol. (1989) 340:403-410, describe a non classical 5-hydroxytryptamine receptor, now designated the 5-HT4 receptor, and that tropisetron (ICS 205-930), which is also a 5-HT3 receptor antagonist, acts as an antagonist at this receptor and metoclopramide is an agonist at this receptor.
WO 91/16045 (SmithKline and French Laboratories Limited) describes the use of cardiac 5-HT4 receptor antagonists in the treatment of atrial arrhythmias and stroke.
Metoclopramide has been shown to be effective in treating a poorly functioning bladder, (Scand. J. Urology and Nephrology, 13:79-82 (1979) but this has not been specifically linked to any known action of metoclopramide.
There are reports in the literature of 5-HT4 receptors potentiating contractions in human bladder (Br. J. Pharmacol, 61, 115P) and inhibiting contractions in monkey bladder (2nd International Symposium on Serotonin, Houston, September 1992, page 86).
We have now discovered that a compound which acts as an antagonist at 5-HT4 receptors is of potential use in the treatment of conditions associated with bladder hypersensitivity, such as urinary incontinence, which is often associated with irritable bowel syndrome (IBS) and a compound which acts as an agonist at 5-HT4 receptors is of potential use in the treatment of conditions associated with a poorly functioning bladder, such as urinary bladder hypoactivity following prostectomy. When used herein the term xe2x80x985-HT4 modulatorxe2x80x99 is used to denote antagonists and agonists.
The invention therefore provides a method for the treatment and/or prophylaxis of conditions associated with bladder hypersensitivity and conditions associated with a poorly functioning bladder in mammals, including humans, which method comprises administering to the mammal in need of such treatment and/or prophylaxis, an effective and/or prophylactic amount of a 5-HT4 modulator.
5-HT4 modulators may be identified according to standard methods, such as those described hereinafter, and that described in Naunyn-Schmiedeberg""s Arch Pharmacol. 342, 619-622.